ASCO 2017: Development and validation of a prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer from the phase 3 Prevail clinical trial
The authors of the PREVAIL study, in this post-hoc analysis study, identify predictors of OS regardless of therapy and develop/validate a prognostic model for mCRPC patients.
Patients were randomly divided 2:1 into training (n = 1159) and testing (n = 550) sets. Demographics, disease characteristics, and OS were balanced between the training and testing sets; median OS was 32.7 months for both datasets. They did note that treatment interaction of all the prognostic factors tested negative, indicating that none were predictive of efficacy at baseline.
Using the training set, 23 predefined potential prognostic factors (including treatment) were analyzed in a multivariable Cox model to predict OS. The final multivariable model included 11 prognostic factors: prostate-specific antigen, treatment, hemoglobin, neutrophil-lymphocyte ratio, liver metastases, time from diagnosis to randomization, lactate dehydrogenase, ≥ 10 bone metastases, pain, albumin, and alkaline phosphatase. Treatment related variables were not found to be significant.
The predictive accuracy was then assessed in the testing set. The testing set was stratified based on risk score tertiles (low, intermediate, high) and binary (high and low) and OS was analyzed using Kaplan-Meier methodology. Median OS for the low-, intermediate-, and high-risk groups in the testing set were: not yet reached, 34.2 months, and 21.1 months. In the binary mode, results were similar for low and high risk groups: not yet reached and 26.1 months.
The final model and its derivation are not included in the abstract. It will be provided in the final manuscript for external validation.
Clearly, there exists significant heterogeneity within the mCRPC population. As such, not all patients likely warrant the same therapy. This prognostic model, based on variables routinely collected, already identified clear stratification in different patient populations.
While interesting, unfortunately, it does not add much clinical value. A better assessment would have been an analysis of only enzalutamide-treated patients to identify predictors of response.
Presented By: Andrew J. Armstrong, MD, ScM, Division of Medical Oncology and Urology, Duke Cancer Institute, Duke University, Durham, NC
Co-Author(s): Ping Lin, Celestia S. Higano, Cora N. Sternberg, Guru Sonpavde, Bertrand F. Tombal, Arnoud J. Templeton, Karim Fizazi, De Phung, Elaine K Wong, Andrew Krivoshik, Tomasz M. Beer
Institution(s): Medivation, Inc., San Francisco, CA; University of Washington Fred Hutchinson Cancer Center, Seattle, WA; San Camillo Forlanini Hospital, Rome, Italy; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; Cliniques universitaires Saint-Luc, Brussels, Belgium; Department of Medical Oncology, St. Claraspital and Faculty of Medicine, University of Basel, Basel, Switzerland; Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif, France; Department of Biometrics, Astellas Pharma Europe B.V., Leiden, Netherlands; Astellas Pharma, Inc., Northbrook, IL; Knight Cancer Institute, Oregon Health & Science University, Portland, OR
Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto
Twitter: @tchandra_uromd
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA
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